GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Prognostic value of Bcl-2 in breast cancer.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e11527-e11527
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e11527-e11527
    Abstract: e11527 Background: Breast cancer is a heterogeneous disease with prognostic factors used by the oncologists to decide the treatment. Bcl2 is an antiapoptotic proto-oncogen involved in DNA break process that has been defined historically as a poor prognostic factor. This study was conducted to confirm whether or not bcl-2 is an independent prognostic factor. Methods: In this study, we have reviewed all patients who were diagnosed at our hospital between January 2007 and December 2008 (99 patients). Inclusion criteria were patients diagnosed of breast cancer whose anatomopathological report showed bcl-2 status as well as the rest of the parameters measured. The parameters measured were age, past medical history, menopausal status, TNM, hormone receptors, HER2, p53, Ki67, bcl-2, treatment applied, date of relapse (if any), date of death ( if occurred). All of them characterized by centralization measures. We conducted an analysis of prognostic factor that influenced survival. Results: The average age of diagnosis is 54.6 years (30-94 years). 42.4% were premenopausal. The average tumor size was 2.59 cm ( 0.5-7.5 cm). 81.8% had positive estrogen receptors. 92% were HER2 negative by inmunohistochemistry. 62.6% were p53 negative. Bcl-2 was 84.8% positive. The distribution by stage at diagnosis was: stage I 26.3%; stage II 49.5%; stage III 22.2%. Disease free survival for patients bcl2(+) was 45.6 months versus 22.6 months for patients bcl2 (-) (0.12-22.2; p: 0.00125). Overall survival for the group bcl2(+) was 48 months (41.6-54.3) and bcl2 (-) was 48.24 months (42.48 to 54). Conclusions: We can state that bcl2 is not an independent prognostic factor. Despite the value in other diseases, the determination of bcl-2 by inmunohistochemistry in breast cancer in stages I, II and III at the moment of the diagnosis does not provide any prognostic information.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.e11527
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Safety and efficacy results from the expansion phase of the first-in-human study evaluating TGFβ inhibitor SAR439459 alone and combined with cemiplimab in adults with advanced solid tumors.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 2524-2524
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 2524-2524
    Abstract: 2524 Background: SAR439459 (SAR459) is a human anti-TGFβ monoclonal antibody that neutralizes all isoforms of TGFβ. In preclinical models, combining SAR459 with an anti-PD-1 showed improved anti-tumor activity compared to SAR459 single agent. In the dose escalation, acceptable tolerability was observed, the MTD was not reached and the preliminary RP2D was 22.5mg/kg Q3W when combined with cemiplimab (CEMI; S. Williamson et al. J Clin Oncol 39, 2021[suppl 15; #2510]). Reduction of plasma TGFβ was ≥90% at doses ≥0.25mg/kg Q2W, with a trend of a decrease in intra-tumoral TGFβ (D. Robbrecht et al. JITC 2021;9 [suppl 2; #250] ). Here we report safety and efficacy results of the dose expansion. Methods: The expansion phase of this open-label, phase 1/1b study aimed to determine the optimal dose of SAR459 (7.5 mg/kg or 22.5 mg/kg Q3W) in patients (pts) with advanced melanoma (MEL) resistant to anti-PD(L)1 therapy (Part 2A); and the ORR (confirmed responses) in all treated pts with SAR459 22.5 mg/kg + CEMI 350 mg Q3W in pts with MEL, Non-small Cell Lung Cancer (NSCLC), or Hepatocellular Carcinoma (HCC), resistant to anti-PD(L)1; as well as in pts with mesenchymal Colorectal Cancer (CRC) or Urothelial Cancer (UC), anti-PD(L)1 naïve (Part 2B). Results: From October 2019 to September 2021, 109 pts with ECOG PS 0-1 enrolled in Part 2A (14) and Part 2B (95). Overall, the median age was 63 years and 83% of pts received up to 3 prior treatment lines for advanced disease (range 1-8). Based on preliminary data, the ORR in Part 2B was 8% (Table). No significant association between clinical response and plasma TGFb level at baseline or modulation upon treatment was observed. The correlation between tumor TGFb level and clinical benefit is inconclusive due to limited number of tumor biopsies. No response was observed in Part 2A. Overall, 100% of pts had at least one treatment emergent adverse event (AE), 67% were G≥3, 34% related G≥3, 17% G5, and 4% related G5. The limited number of patients treated with SAR459 alone at the RP2D did not allow to demonstrate added toxicity due to the combination. Overall, 51 pts (47%) reported hemorrhagic AE of any grade, 8 pts (7%) had G≥3 and 5 pts (5%) had fatal outcome. The rate of bleeding and severe hemorrhagic AE was higher in HCC pts compared to the other cohorts: 11/14 (79%) pts had a hemorrhagic AE, of which 3 (21%) G≥3 and fatal. An exploratory analysis showed a trend for higher frequency of any grade SAR459-related and fatal hemorrhagic AE in patients with higher exposure. Conclusions: The NCT03192345 study was discontinued due to a lack of efficacy, and a high bleeding risk particularly in pts with HCC. Clinical trial information: NCT03192345. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.2524
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Abstract 5045: Predictive factors for successful growth of patient derived xenograft (PDX)
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. 5045-5045
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 5045-5045
    Abstract: Background: PDXs have become a core component of translational cancer research. Developing these models can become challenging since little is known about which factors influence engraftment rates. We sought to determine which clinical, pathological or molecular factors may predict a higher chance of success for PDX development. Methods: Between March 2017 and August 2019, biopsies obtained from patients with primary or metastatic cancer were implanted into athymic nude mice. Statistical analyses were performed to identify factors that could correlate with final engraftment defined as tumor volume of 150 mm3 in at least three consecutive measurements. We focus on clinical (patient factors) pathological (tumor sample) and molecular characteristics (tumor sample). Information regarding sampling process was also analyzed. Results: 440 tumor samples were collected and implanted. 15 failed due lack of tumor cells. Of 425 tumor-positive samples, 143 PDXs achieved successful growth at time of analysis. The following clinical characteristics were correlated with engraftment success: systemic steroid administration within 2 weeks of sampling (45.5% (30/66) within the steroids-receiving group achieved growth vs 31% (113/359) no-steroids) (p: 0.027). High neutrophils/lymphocytes (NLR) ratio ( & gt;5) (42.3% (47/111) of tumors with NLR & gt;5 achieved growth vs 30% (96/313) in the NLR & lt;5 group; P:0,018). Regarding pathological tumor characteristics, higher ki67 levels were correlated with better engraftment rates (Low (Ki67 & lt;15%): 10% (5/46) vs. Medium (Ki67:15-30%): 25% (7/28) and high (Ki67 & gt;30%): 34% (16/47) (p:0.029). The presence of mucinous cells (signet ring cells) was also correlated with higher chance of tumor engraftment (50% (19) vs. 32% (124/387) (p: 0.022). Negativity for estrogen receptors could also be a positive predictive marker (14% (8/57) of ER+ achieved growth vs 46.7% (7/15) ER negative (p: 0.011). Lastly, sampling source (either primary of metastatic tumors) was not correlated with successful growth. Conclusions: tumors with higher Ki67, mucinous features and ER expression negative have higher chance of PDX development. Some clinical characteristics can also interfere with PDXs development such as use of steroids or NLR. Citation Format: Tatiana Hernandez, Natalia Baños, Victoria Bonilla, Laura del Puerto, Bernard Doger, Jesus Garcia-Foncillas, Michael Wick, Victor Moreno. Predictive factors for successful growth of patient derived xenograft (PDX) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5045.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2020-5045
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Abstract 3435: Identification of potential biomarkers of response to OMO-103, a first-in-modality pan-MYC inhibitor, in patients with advanced solid tumors
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 3435-3435
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 3435-3435
    Abstract: Background: MYC is a key transcription factor driving and maintaining human tumors. Since MYC has long been perceived as an “undruggable” target, to date, there is still no MYC inhibitor approved for clinical use. However, we designed and validated Omomyc, a MYC dominant negative mini-protein, demonstrating its potent therapeutic impact in various mouse models of cancer. Importantly, a Phase 1 study testing OMO-103, an Omomyc-based mini-protein developed by Peptomyc S.L., was successfully completed in 2022. Here, we present the main findings of the study and associated biomarker program. Material and Methods: A phase I dose escalation study was performed in all-comers solid tumor patients, with a 3+3 design of 6 dose levels ranging from 0.48 to 9.72mg/kg, as a weekly 30-min i.v. infusion. Tumor and liquid biopsies were collected at screening, upon and at the end of treatment, to assess different biomarkers of drug activity. Results: 22 patients with advanced solid tumors were included and 18 patients were considered evaluable for response by CT scan. Of these, 9 achieved SD. The PK analysis revealed a plasma half-life of & gt;40h. No ADAs were detected in any of the patients. Drug pharmacodynamics supported target engagement, as demonstrated by Digital Spatial Profiling analysis showing shut down of MYC transcriptional signature in patients’ tumor biopsies. In addition, a distinctive pharmacodynamic cytokine signature that correlated with stable disease was found through liquid biopsies already 3 to 4 weeks before CT scan. Importantly, a cytokine signature was also identified as being predictive of disease stabilization at baseline and could help stratify patients in upcoming additional clinical studies. Finally, several anti-tumor immune related markers were also found modulated upon OMO-103 treatment. Conclusion: OMO-103 demonstrates a favorable safety profile, with encouraging signs of activity supported by predictive and pharmacodynamic biomarkers worthy of further investigation. Citation Format: Marie-Eve Beaulieu, Elena Garralda, Sílvia Casacuberta-Serra, Sandra Sandra Martínez-Martín, Emiliano Calvo, Víctor Moreno, Sergio López-Estévez, Laia Foradada, Guzman Alonso, Elena Corral, Bernard Doger, Tatiana Hernández, Judit Grueso, Íñigo Íñigo González-Larreategui, Erika Serrano del Pozo, Hugo Thabussot, Virginia Castillo Cano, Mariano F. Mariano F. Zacarías-Fluck, Jastrinjan Kaur, Fabio Giuntini, Jonathan R. Whitfield, Josefa Morales, Manuela Niewel, Laura Soucek. Identification of potential biomarkers of response to OMO-103, a first-in-modality pan-MYC inhibitor, in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3435.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-3435
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Abstract CT176: Pharmacokinetic/pharmacodynamic (PK/PD) relationships of the novel Treg depleter RG6292 in Phase Ia and Ib studies in patients with solid tumors
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 8_Supplement ( 2023-04-14), p. CT176-CT176
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 8_Supplement ( 2023-04-14), p. CT176-CT176
    Abstract: INTRODUCTION: Activated Tregs in the tumor micro-environment are correlated with poor outcomes, and are considered as key players in tumor immune-escape. So far, Treg depletion has not been successful in patients, either because adequate Treg depletion was not achieved or because Teff cells have either been impacted or depleted as well. RG6292 is the first anti-human CD25 antibody developed to specifically deplete human Tregs while preserving IL-2R STAT5 signaling and Teff activity. It has been optimized for ADCC and selective depletion of cells with high CD25 density (Treg). MATERIALS and METHODS: Adult patients with advanced solid tumors were given RG6292 i.v. Q3W as monotherapy (S1: NCT04158583) or in combination with atezolizumab 1200 mg Q3W (S2: NCT04642365) in a Ph1 dose escalation study. 76 pts have been treated at dose levels ranging from 0.3 mg to 165 mg in S1 and 48 pts at dose levels ranging from 0.3 mg to 160 mg in S2. In both studies a Bayesian logistic regression model with overdose control guided dose escalation was utilized. Data cutoff was May 27, 2022. Pharmacokinetic and pharmacodynamic analyses were undertaken in peripheral blood and tumor tissue. PK/PD modeling applied to Treg and Teff cells helped characterize and identify the optimal therapeutic window to ensure (1) relevant Treg depletion and (2) limited impact on T effector. RESULTS: RG6292 has a linear and time independent PK with no ADA detected. A Population PK-PD modeling approach was applied to Treg and Teff cells in the periphery. To predict the RG6292 effects in the tumor microenvironment (TME), the PK/PD relationships observed and characterized in the periphery for all cell subpopulations were considered the same, a tumor uptake factor of 15% was considered. At steady-state trough, a 70 mg Q3W dose was predicted to lead to 72% of patients with concentration above the Treg (%CD4) EC50 in tumor and 40% of patients with concentration above the Non-Treg (%CD4) EC50 in plasma. RG6292 induced a dose-dependent peripheral and intratumoral Treg depletion in on-treatment biopsies taken 28 days after initiation of treatment. Treatment did not appear to impact the number nor the functionality of intratumoral CD8 T cells nor any evident effect observed on PDL1 expression. In blood, stable levels of all other immune cells were observed after treatment. Moreover, in both studies a marginal increase of IFNg, CXCL10, IL-10, TNF was observed. No consistent gene expression alterations nor immune signatures could be observed when comparing BSL vs OT biopsies in S1. CONCLUSION: RG6292, consistent with its proposed mechanism of action, induces profound and preferential depletion of Treg cells over CD8+CD25+ in the periphery and in the TME at clinically safe doses between 35-70mg. Further development of RG6292 is currently being explored. Citation Format: Tamara Tanos, Kevin Smart, Valentina Gambardella, Kristoffer Rohrberg, Michael Ong, Maria Esperanza Rodriguez Ruiz, Jean-Pascal Machiels, Miguel Fernández Sanmamed, Josep Tabernero, Anna Spreafico, Daniel Renouf, Stephen Luen, Rachel Galot, Bernard Doger, Emiliano Calvo, Aung Naing, Samira Curdt, Nicolas Staedler, Mike Flores, Enrique Gómez Alcaide, Chiahuey Ooi, Michael Hettich, Sebastian Dziadek, Yuying Xie, Gabriel Schnetzler, Theresa Kolben, Linxinyu Xu, Vaios Karanikas, Christophe Boetsch. Pharmacokinetic/pharmacodynamic (PK/PD) relationships of the novel Treg depleter RG6292 in Phase Ia and Ib studies in patients with solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT176.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-CT176
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Antidrug Antibodies and Drug Development: Challenges in the Immunotherapy Era
    American Association for Cancer Research (AACR) ; 2021
    In:  Clinical Cancer Research Vol. 27, No. 10 ( 2021-05-15), p. 2669-2671
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 27, No. 10 ( 2021-05-15), p. 2669-2671
    Abstract: Novel antibody formats such as bispecifics have increased risk of immunogenicity, impacting safety and efficacy. LY3415244, a novel T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM3)-PDL1 (programmed death (ligand) 1) bispecific caused neutralizing antibody–drug antibodies (ADA) in 12 of 12 patients and required study termination. Novel approaches are needed to ameliorate and manage this undesirable effect of therapeutic antibodies. See related article by Hellmann et al., p. 2773
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-21-0168
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Corrigendum to ‘A phase 1b study of afatinib in combination with standard-dose cetuximab in patients with advanced solid tumours’ [Eur J Cancer 104 (November 2018) 1–8]
    Elsevier BV ; 2019
    In:  European Journal of Cancer Vol. 119 ( 2019-09), p. 198-
    Details
    In: European Journal of Cancer, Elsevier BV, Vol. 119 ( 2019-09), p. 198-
    Type of Medium: Online Resource
    ISSN: 0959-8049
    URL: Article
    DOI: 10.1016/j.ejca.2018.12.018
    RVK:
    XA 42017.A
    RVK:
    XA 42017
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 1120460-6
    detail.hit.zdb_id: 1468190-0
    detail.hit.zdb_id: 82061-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    A phase 1b study of afatinib in combination with standard-dose cetuximab in patients with advanced solid tumours
    Elsevier BV ; 2018
    In:  European Journal of Cancer Vol. 104 ( 2018-11), p. 1-8
    Details
    In: European Journal of Cancer, Elsevier BV, Vol. 104 ( 2018-11), p. 1-8
    Type of Medium: Online Resource
    ISSN: 0959-8049
    URL: Article
    DOI: 10.1016/j.ejca.2018.07.011
    RVK:
    XA 42017.A
    RVK:
    XA 42017
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 1120460-6
    detail.hit.zdb_id: 1468190-0
    detail.hit.zdb_id: 82061-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Initial results from a phase II study (TACTI-002) in metastatic non-small cell lung or head and neck carcinoma patients receiving eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 3100-3100
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 3100-3100
    Abstract: 3100 Background: Eftilagimod alpha (efti) is a soluble LAG-3 protein that binds to a subset of MHC class II molecules to mediate antigen presenting cell (APC) activation and then CD8 T-cell activation. The stimulation of the dendritic cell network and subsequent T cell recruitment with efti may lead to stronger anti-tumor responses than observed with pembrolizumab alone. We hereby report initial results of a phase II trial (NCT03625323). Methods: A predefined number of patients (pts) are recruited into this 3-cohort trial irrespective of PD-L1 expression; part A: 1 st line, PD-X naïve NSCLC; part B: 2 nd line, PD-X refractory NSCLC and part C: 2 nd line PD-X naive HNSCC. The study has a Simon's 2-stage design, with objective response rate (ORR) as primary endpoint. Secondary endpoints include disease control rate, progression free and overall survival, PK, PD and immunogenicity. Additional pts (N2) will be recruited for each part if pre-specified thresholds for ORR are met. Up to 109 pts will be enrolled. Efti is administered as 30 mg subcutaneous injection every 2 wks for 8 cycles and then every 3 wks for 9 cycles with pembrolizumab (200 mg intravenous infusion every 3 wks for up to 2 yrs). The study was approved by ethic committees and institutional review boards. Results: Between 04 Mar 19 and 31 Jan 2020, 48 pts were enrolled and evaluated for safety and exposure. The median age was 66 yrs (range 48-84) and 73 % were male. The ECOG was 0 in 50 % and 1 in 50 % of pts, respectively. Pts received a median of 5 (7) and in total 311 (413) pembrolizumab (efti) administrations, respectively. Three pts (6.3 %) discontinued study treatment due to AEs. The most common ( 〉 10%) adverse events (AEs) being cough (31 %), asthenia (23 %), decreased appetite (19 %), fatigue (19 %), dyspnea (17 %), diarrhea (15 %) and constipation 13 %). From part A all pts (n = 17) were evaluated. Eight pts (47 %) had a partial response (iPR) and six (35 %) had stable disease according to iRECIST representing an ORR (DCR) of 47 % (82 %). irPRs were observed in all different PD-L1 groups ( 〈 1%; ≥ 1 % ≤49 %; ≥ 50 %). Ten (10; 59 %) pts are still on therapy (8+ months). In part C stage 1 15/18 pts are evaluable and six (40 %) had an iPR to date. Conclusions: Efti in combination with pembrolizumab is safe and shows encouraging antitumor activity in all comer PD-L1 1 st line NSCLC and 2 nd line HNSCC. Stage 2 has opened for both parts. Clinical trial information: NCT03625323 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.3100
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Results from a phase II study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in patients with PD-L1 unselected metastatic non-small cell lung carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 9046-9046
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 9046-9046
    Abstract: 9046 Background: Eftilagimod alpha (efti) is a soluble LAG-3 protein that binds to a subset of MHC class II molecules to mediate antigen presenting cell (APC) activation and CD8 T-cell activation. The stimulation of the dendritic cell network and subsequent T cell recruitment with efti may lead to stronger anti-tumor responses in combination than observed with pembrolizumab alone. We hereby report results of the 1st line non-small cell lung carcinoma (NSCLC) part of the phase II trial (NCT03625323). Methods: Patients (pts) with untreated, immunotherapy naïve, advanced NSCLC unselected for PD-L1 expression were recruited into part A. The study used a Simon's 2-stage design (17 pts planned for stage 1 and 19 pts for stage 2), with objective response rate (ORR) by iRECIST as the primary endpoint (EP). Secondary EPs include tolerability, disease control rate (DCR), progression free survival (PFS), overall survival (OS), PK, PD and immunogenicity. Efti is administered as 30 mg subcutaneous injection every 2 wks for 8 cycles and then every 3 wks for 9 cycles with pembrolizumab (200 mg intravenous infusion every 3 wks for up to 2 yrs). Imaging was performed every 8 weeks locally and with blinded independent central review (BICR) retrospectively. The study was approved by ethic committees and institutional review boards. Results: In total 36 pts were enrolled. At data cut-off (Jan 2021; median FU of 14 months), the median age was 69 yrs (range 53-84) and 69 % were male. The ECOG PS 0 and 1 was 42% and 58% respectively. Patients had squamous (42%) and non-squamous (58%) NSCLC and 95% presented with metastatic disease. All PD-L1 subgroups (TPS 〈 1 %, ≥ 1 % to ≤49 %; ≥50 %) were represented with 36% pts having ≥50% TPS. Pts received a median of 7.0 (range 1 – 31) pembrolizumab and 11.5 (range 1-22) efti administrations. Responses as per BICR and local read are shown in the table. ORR (local, iRECIST) by different PD-L1 subgroups was 27% for pts with TPS 〈 1%, 39 % for TPS ≥1 %and 54% for ≥50 % TPS. Median PFS (n=36) was 8.2 months while median OS was not yet reached. The most common ( 〉 20 %) treatment emergent adverse events (AEs) were asthenia (47 %), cough (36 %), decreased appetite (36 %), dyspnea (32 %), pruritus (31 %), fatigue (28 %), diarrhea (25 %), anemia (25 %), constipation (25 %) and back pain (22%). Two patients discontinued treatment due to adverse reactions (Grade 4 immune-mediated hepatitis, Grade 3 AST+ALT increase). Conclusions: Efti in combination with pembrolizumab is safe and shows encouraging antitumor activity in 1st line advanced NSCLC patients across all PD-L1 (TPS) levels. Clinical trial information: NCT03625323. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.9046
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...